Patent GB-667786-A (GB)
Title: Production of amino hydroxy butyric acids
Filed: 1949-07-04
Abstract: a -Amino-b -hydroxy butyric acids are prepared by passing a vapour mixture of one molecular equivalent of a 2-alkoxy-1-propanol and an oxygen-containing gas in amount comprising not more than 0.5 molecular equivalent of free oxygen into contact with metallic silver at a reaction temperature between 350 DEG  and 550 DEG  C., cooling the effluent vapours to condense the a  - alkoxy - propionaldehyde which is formed, admixing the a -alkoxy-propionaldehyde with an aqueous solution of ammonium cyanide or an aqueous solution of another ionizable inorganic cyanide and ammonia or an ammonium salt thereby effecting a reaction with formation of an a -amino-b -alkoxy-butyronitrile, and hydrolysing the latter by heating with an aqueous solution of a strong mineral acid to form a -amino-b -hydroxybutyric acids. The product is a mixture of dl-threonine and dl-allothreonine, the former amounting usually to about 50 per cent of the mixture, from which they may be separated by fractional crystallization.  The a -alkoxy propionaldehydes and a  - amino - b - hydroxy butyronitriles are stated to be new compounds.  The preferred 2-alkoxy-1-propanol starting materials contain less than 8 carbon atoms, e.g. 2-methoxy-, 2-ethoxy-, 2-propoxy-, 2-isopropoxy-, 2-butoxy- or 2-sec-butoxy-1-propanol.  The oxidation to a -alkoxy-propionaldehyde is preferably effected at such a temperature and rate of flow that not more than 30 per cent of the alkoxy-propanol and alkoxy-propionaldehyde is thermally decomposed; the silver catalyst may be in the form of one or more screens, or a bed of turnings or particles on a carrier such as pumice or brick-ware.  The condensed oxidation products are distilled to separate an aqueous azeotrope containing the aldehyde and recover unchanged alcohol for further use.  The aqueous aldehyde solution or dry aldehyde recovered therefrom may be used to form the butyronitrile in the next step.  The cyanide reactant is preferably sodium or potassium cyanide but calcium cyanide or hydrogen cyanide can also be used; ammonium salts specified for use therewith are the halides such as the chloride or bromide and ammonium sulphate.  If desired, ammonium cyanide may be used directly as the ammonium salt and cyanide starting materials.  The butyronitrile forming reaction occurs on admixing the reagents at room temperature or lower, the mixture being warmed subsequently, e.g. to 40-100 DEG  C. to complete the reaction; the theoretical proportions of reactants are normally used.  The resulting amino-alkoxy-butyronitrile may be recovered from the product by distilling off water and extracting the nitrile from the residue by means of an organic solvent, e.g. alcohol.  Hydrolysis of the nitrile is preferably effected by refluxing with a constant boiling aqueous hydrobromic acid solution.  Aqueous hydrochloric or sulphuric acid may also be used.  The hydrolysis product is treated to remove the mineral acid and the residual mixture of amino-hydroxybutyric acids allowed to crystallize out.  In examples: (1) and (3), 2-methoxy-1-propanol is oxidized by means of air over a silver screen catalyst at temperatures of 370-430 DEG  C. and the products condensed to provide an aqueous solution of a -methoxy propionaldehyde which is reacted with an aqueous solution of ammonia, ammonium chloride and potassium cyanide, the resulting a  - amino - b - methoxy butyronitrile hydrolysed by being refluxed with aqueous hydrobromic acid and the amino hydroxy butyric acids so formed isolated by distilling off hydrobromic acid under vacuum and crystallizing the residue from methanol; (2) similarly, 2-isopropoxy-1-propanol is oxidized to the aldehyde which is converted into a -amino-b -isopropoxy-butyronitrile and the latter hydrolysed to the amino-hydroxy acids.